The synthesis of .gamma.-emitting halogenated steroids is not unusually difficult, but the synthesis of such compounds which also have biological activity has, for the most part, resisted intensive efforts. The complex information which is encoded within the steroid hormone molecule is contained within such a small structure that analogs labelled, for example, with the useful isotopes of iodine, are usually biologically inactive. The radiohalogen is so bulky compared to the steroid nucleus that it interferes with the exquisitely sensitive interaction of the hormone with its receptor. These difficulties have limited the development of the useful biological and clinical probes of hormone action and to date, the only radioiodonated, biologically active steroids that have been synthesized are estrogens.
Hochberg in U.S. Pat. No. 4,465,676 describes 16.alpha.-radiohalogenated-3,17.beta.-dihydroxysteroidal estrogens, including the 16.alpha.-iodo analog of estradiol, and their use in estrogen receptor assays, radioimmunoassays, in vivo imaging of tissue having estrogen receptor activity, and for therapeutic treatment of tumors which have estrogen receptor activity. Additionally, the E-17.alpha.-[2-iodovinyl]analogs of estradiol have been prepared which bind to the estrogen receptor and concentrate in estrogen target tissues. See Hansen et al., J Nuclear Med. (1982), 23, 431 and Jogoda et al., J. Nuclear Med. (1984), 25, 472.
The quantification of the estrogen receptor is an important adjunct in determining therapy in patients with carcinoma of the breast and 16.alpha.-[.sup.125 I]iodoestradiol is frequently used for the active detection of this trace protin. More recently, it has become clear that the measurement of the progesterone receptor (an estrogen-induced protein) in addition to the estrogen receptor, yields more accurate guidelines for hormonal therapy of breast cancer. Clark et al., Breast Cancer Res. Treat. (1983), 3, 157.
A number of steroids have been prepared as potential ligands for the progesterone receptor and tested for their ability to compete with the binding of [.sup.3 H]17.alpha.,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione (R5020) (which is the standard ligand for this receptor, see Philibert et al., Endocrinol, (1974), 94, 627). Many of these steroids did not cause any displacement of the tracer until their added concentration exceeded the K.sub.d of R5020 by a very large factor, for example, 10,000. These compounds, therefore, were not good ligands of the progesterone receptor. However, it has been found that the 16.alpha.-iodo and both the E and Z 17.alpha.-(2-iodovinyl)analogs of 19-nortestosterone bind the progesterone receptor with high affinity.